ROLE OF NF-κB TRANSCRIPTION FACTOR ACTIVATION IN THE PROCESSES OF CONNECTIVE TISSUE COMPONENTS DEGRADATION IN SKELETAL MUSCLES UNDER METABOLIC SYNDROME

Abstract

Connective tissue, encompassing both cellular and non-cellular elements, plays an important role in the progression of numerous pathological processes across various organs and tissues. Within skeletal muscle tissue, the extracellular matrix not only plays a structural and supporting function, but it is a complex multicomponent system that performs a number of regulatory functions. At present, the effect of activation of the transcription factor NF-κB on the quantitative and qualitative composition of the components of the extracellular matrix in skeletal muscles under metabolic syndrome development is insufficiently studied. The aim of this work is to study the effect of ammonium pyrrolidinedithiocarbamate on the concentration of glycosaminoglycans, the concentration of individual fractions of glycosaminoglycans, the content of free L-oxyproline and sialic acids in the biceps femoris muscle of rats under metabolic syndrome. The study was conducted on 24 male Wistar rats weighing 200-260 g, which were randomly divided into 4 groups of 6 animals each. The first was control; the second made up the metabolic syndrome modeling group. Metabolic syndrome was reproduced by adding a 20% fructose solution to the standard vivarium diet as the only source of drinking water. Metabolic syndrome was modelled for 60 days. The third group received ammonium pyrrolidinedithiocarbamate administration at a dose of 76 mg/kg intraperitoneally (i/p) three times a week for 60 days. The fourth group underwent combined treatment involving the administration of both ammonium pyrrolidinedithiocarbamate and metabolic syndrome modeling. In a 10% homogenate of the biceps femoris muscle, the total concentration of glycosaminoglycans, the concentration of the heparin-heparan fraction of glycosaminoglycans, the keratan-dermatan fraction of glycosaminoglycans, the chondroitin fraction of glycosaminoglycans, and the content of free L-oxyproline and sialic acids were assessed. The introduction of ammonium pyrrolidinedithiocarbamate under metabolic syndrome modelling led to a decrease in the total concentration of glycosaminoglycans by 9.2% compared to the metabolic syndrome group. Under these conditions, the concentration of the heparin-heparan fraction increased by 121.1%, the keratan-dermatan fraction decreased by 32.8%, and the concentration of the chondroitin fraction decreased by 38.7% compared to the metabolic syndrome group. The concentration of free L-oxyproline and sialic acids in the biceps femoris muscle decreased by 19.8% and 24.4%, respectively, compared to the metabolic syndrome group. Blockade of activation of the transcription factor NF-κB by intraperitoneal administration of ammonium pyrrolidinedithiocarbamate against the background of metabolic syndrome modelling leads to a decrease in the depolymerization of glycoproteins and proteoglycans, reduces the intensity of collagenolysis and leads to a redistribution of concentrations of individual fractions of glycosaminoglycans, characterized by an increase in the content of the heparin-heparan fraction and a decrease in chondroitin and keratan-dermatan fractions in the biceps femoris muscle of rats.